PROJECT SUMMARY Non-prescription opiate use in adolescents and young adults is epidemic in our country and overdose-related fatalities are rising. Adolescents and young adults in justice settings (AYAJS) have some of the highest rates of opioid use disorder (OUD), with national rates approaching 20%. The majority of AYAJS engage in problematic non-opioid substance use, which is a critical risk factor for OUD. Non-opioid substance use disorders (SUDs) and OUD, in turn, are two of the most important predictors of subsequent re-involvement in juvenile or criminal justice systems. Seattle Children?s Hospital (SCH), University of Washington (UW), and Washington State Juvenile Rehabilitation (WSJR) will collaboratively evaluate OUD prevention interventions of varying intensities based on the Adolescent Community Reinforcement Approach with Assertive Continuing Care (ACRA/ACC). Multiple studies have established effectiveness of ACRA/ACC in reducing SUD; however none have evaluated it as an OUD prevention strategy. SUD is incredibly common and costly among AYAJS; thus ACRA/ACC- based approaches are likely to be effective and cost-beneficial OUD prevention strategies for this group. However, we need to determine the optimal intensity of an ACRA/ACC-based OUD prevention intervention for AYAJS with and without non-opioid SUD, as these groups are likely to have differing prevention needs. We will use Sequential Multiple Assignment Randomized Trial (SMART) to construct high-quality adaptive interventions (AIs) containing ACRA/ACC-based OUD prevention strategies of different intensity levels among SUD and non-SUD youth. In our 2-year UG3 phase, we will collaboratively plan for a SMART experiment, i.e.: finalize infrastructure, recruitment, intervention, and data collection procedures; and create infrastructure for sustainable future implementation of effective interventions after the UH3 full trial (UG3 Aim 1). We will conduct a pilot with 40 AYAJS to assess feasibility of protocols and procedures, recruitment, engagement, and retention strategies in anticipation of full trial (UG3 Aim 2). In our 3-year UH3 phase, we will conduct a SMART trial with 430 AYAJS aged 16-25 from all WSJR institutions to evaluate ACRA/ACC-based OUD prevention interventions of various intensity levels among SUD and non-SUD youth (UH3 Aim 1). We will administer self- report electronic surveys at baseline, 1, 3 & 6 months to collect cost and outcomes data on primary outcomes (initiation and escalation of use measured by number of days and frequency of use of any substances) and secondary outcomes (number of days/frequency of use of specific substances including opioids, others); we will use administrative data to measure recidivism. Our UH3 Aim 2 will be to conduct comprehensive cost analyses to estimate the resources required to implement our ACRA-based interventions. Our proposal is responsive to the RFA, innovative in its degree of partnership with WSJR as well as in its rigorous and pragmatic SMART design. It is also high impact in that it is highly likely to prevent OUD for one of the most vulnerable youth populations in our country.